Transcript Mammals have 4 clusters of Hox genes

Two clusters of Drosophila
homeotic genes:
Antennapedia-complex (ANT-C)
Bithorax-complex (BX-C)
Hox genes
Mammals have 4 clusters of
Hox genes
Most likely produce by
duplications of an ancestral
Hox gene complex
Maintenance of Homeotic Genes
Expression Patterns
Trithorax-group:
Maintain homeotic genes in ON state.
Maintain active chromatin structure.
Polycomb-group:
Maintain transcriptional SILENCE of homeotic genes.
Maintain repressive chromatin structure.
Both involve covalent modifications of histones.
(Acetylation/Deacetylation & Methylation)
Collectively, help to maintain determined states of cells.
Mouse Hox gene expression
Hoxc-8 mutant
L1 = 1st lumbar vertebra
WT: L1 does not have ribs
Hoxc-8- mutant: L1 develops
like a more anterior vertebra
(homeotic phenotype)
Hoxc-8- mutants are viable
and have additional
phenotypes
Subdivision of vertebrate hindrain by Hox gene
expression
r = rhobdomere
r2
r4
r3
r5
r7
Evo-Devo
Changes in adult bodies are due to changes in development.
Animal bodies have a modular construction:
Made up of serially repeated parts
Ex: Multiple segments in insects
Multiple vertebrae in vertebrates
Major themes in evolution
 Change number of repeating units
 Modify forms & specializations of a subset of
repeating units
In most cases, this does not involve the evolution of new genes
Most developmental changes due to:
 Changes in patterns of expression of Hox & other genes that
control pattern formation.
• This is caused by changes in their regulatory elements
 Changes in the regulatory regions of genes that they regulate
(effector genes).
head
neck
Hoxc6 expression marks
boundary between neck
and trunk vertebrae
trunk
Based on patterns of gene expression, it appears that insect
wings evolved from gill branches of aquatic crustaceans
Evidence: Apterous & nubbin are required for fly wing development.
Homologs of these genes are expressed in the respiratory lobes
of modern crustacean limbs.
Cis-regulatory region of a
wing-promoting gene
These Hox proteins suppress wing formation by repressing this wing-promoting gene
By changing which effector genes are regulated
by Ubx, different forms of insect hindwing have
evolved from the ancestral hindwing
effector genes
How are the different patterns on
butterfly wings formed?
Some, but not all
butterfly wings have
eyespots
Expression of Distal-less
(a homeodomain TF) in
butterfly wing imaginal discs
correlates with presence or
absence of eyespots in
different species.
Distal-less expression marks
center of future eyespots
Spalt protein
Engrailed protein
Concentric circles of
pigmented scales due to
expression of other
regulatory genes in
response to Distal-less
GDF5 (a TGFb-family protein, similar
to fly DPP) expression marks where
joints will develop in digits
Scleraxis (a conserved TF)
expression marks where tendons in
limbs & digits will develop
BMP4 (a TGFb-family protein)
expression marks tissue in between
digits that will be lost by apoptosis
Patched (homolog of fly segment
polarity gene) expression marks where
feather buds will develop in chick
embryos.
Eyeless = selector gene for eye development
Ectopic expression of eyeless
ectopic development of eye tissue
Mouse gene: Small eyes
Humans: Aniridia